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基因表达谱和生物信息学分析揭示了脊索瘤在肿瘤坏死因子-α治疗前后的关键分子特征。

Gene expression profile and bioinformatics analysis revealed key molecular characteristics of chordoma-before and after TNF- a treatment.

作者信息

Xu Guoyong, Liu Chong, Liang Tuo, Zhang Zide, Jiang Jie, Chen Jiarui, Xue Jiang, Zeng Haopeng, Lu Zhaojun, Zhan Xinli

机构信息

Guangxi Medical University.

Spine and Osteopathy Ward, The First Affiliated Hospital of Guangxi Medical University, Nanning, PR China.

出版信息

Medicine (Baltimore). 2020 Jan;99(3):e18790. doi: 10.1097/MD.0000000000018790.

Abstract

BACKGROUND

Chordoma is a rare malignant tumor with limited treatment. Recent studies have shown that the proliferation and invasion ability of chordoma after Tumor necrosis factor alpha (TNF-α) treatment is enhanced, which may activate the gene pathway involved in the development of chordoma. This study tends to identify differentially expressed genes (DEGs) before and after treatment of TNF-α in chordoma cell line, providing a new target for future molecular therapy of chordoma.

METHODS

The gene expression profile of GSE101867 was downloaded from the Gene Expression Omnibus database, and the differentially expressed genes were obtained using GEO2R. Based on the CLUEGO plugin in Cytoscape, DEGs functionality and enrichment analysis. A protein-protein interaction (PPI) network was constructed using Cytoscape based on data collected from the STRING online dataset. The Hub genes are selected from the CytoHubba, the first 20 genes that coexist with the KEGG tumor-related pathway.

RESULTS

A total of 560 genes, including 304 up-regulated genes and 256 down-regulated genes, were selected as DEGs. Obviously, GO analysis shows that up-regulated and down-regulated DEGs are mainly enriched in biological processes such as synaptic tissue, cell adhesion, extracellular matrix organization and skeletal system development. DEGs are mainly enriched in tumor-associated pathways such as Pi3k-akt Signal path, Rap1 signal path. Three key genes were identified: PDGFRB, KDR, FGF2. All of these genes are involved in the tumor-associated pathways described previously.

CONCLUSION

This study is helpful in understanding the molecular characteristics of chordoma development. Hub genes PDGFRB, KDR, FGF2 and pi3k-akt signaling pathway, Rap1 signaling pathway will become a new target for the future treatment of chordoma.

摘要

背景

脊索瘤是一种治疗手段有限的罕见恶性肿瘤。最近的研究表明,肿瘤坏死因子α(TNF-α)治疗后脊索瘤的增殖和侵袭能力增强,这可能激活了参与脊索瘤发生发展的基因通路。本研究旨在鉴定脊索瘤细胞系中TNF-α治疗前后的差异表达基因(DEGs),为未来脊索瘤的分子治疗提供新靶点。

方法

从基因表达综合数据库下载GSE101867的基因表达谱,使用GEO2R获得差异表达基因。基于Cytoscape中的CLUEGO插件进行DEGs功能和富集分析。利用Cytoscape基于从STRING在线数据集收集的数据构建蛋白质-蛋白质相互作用(PPI)网络。从CytoHubba中选择枢纽基因,即与KEGG肿瘤相关通路共存的前20个基因。

结果

共筛选出560个基因作为DEGs,其中上调基因304个,下调基因256个。显然,基因本体(GO)分析表明,上调和下调的DEGs主要富集在突触组织、细胞粘附、细胞外基质组织和骨骼系统发育等生物学过程中。DEGs主要富集在Pi3k-akt信号通路、Rap1信号通路等肿瘤相关通路中。鉴定出三个关键基因:血小板衍生生长因子受体β(PDGFRB)、激酶插入域受体(KDR)、成纤维细胞生长因子2(FGF2)。所有这些基因都参与了先前描述的肿瘤相关通路。

结论

本研究有助于了解脊索瘤发生发展的分子特征。枢纽基因PDGFRB、KDR、FGF2以及pi3k-akt信号通路、Rap1信号通路将成为未来脊索瘤治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b0d/7220412/1658c8f6ba1c/medi-99-e18790-g001.jpg

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